Cardiovascular prosthetic devices and implants with porous systems

ABSTRACT

Novel cardiovascular prosthetic devices or implants having many useful cardiovascular applications comprise a porous surface and a network of interconnected interstitial pores below the surface in fluid flow communication with the surface pores. Tissue forms a smooth thin adherent coating or self-determining thickness on the porous surface making it resistant to the formation of the blood clots normally associated with the presence of foreign bodies in the blood stream. The device has particular utility in heart valves, pacemaker electrodes, blood pumps, blood stream filters, an artificial pancreas, vascular access tubes, small and large bore vascular grafts, blood pump diaphragms and vascular and intracardiac patches.

"This application is a continuation of copending application Ser. No.486,796 filed June 30, 1983 now U.S. Pat. No. 4,627,836), which is adivision of application Ser. No. 351,526 filed Feb. 23, 1982 (now U.S.Pat. No. 4,459,252), which is a division of application Ser. No. 095,965(now U.S. Pat. No. 4,355,426), which is a division of application Ser.No. 824,296 filed Aug. 15, 1977 (now U.S. Pat. No. 4,281,669), which isa continuation-in-part of application Ser. No. 683,382 filed May 5, 1976(now U.S. Pat. No. 4,101,984)."

FIELD OF INVENTION

This invention relates to novel prosthetic devices and implants forcardiovascular use.

BACKGROUND TO THE INVENTION

It is well known that the introduction of foreign bodies into the bloodstream, for example, the polished metal surfaces of artificial heartvalves, tends to cause the formation of blood clots which may breakloose and embolize to various parts of the body. Such thromboembolicproblems have led to the administration of anticoagulants to patientswith artificial heart valves. The effects of these anticoagulants on theblood clotting mechanism cause difficulties in stopping the flow ofblood through even a minor flesh wound. In addition, flexible plasticconduits are used for vascular graft purposes and such surfaces also arethrombogenic.

Attempts have been made to overcome the thromboembolic problems ofpolished metal heart valves by providing a porous fabric covering overblood-engaging metal parts. When such porous fabrics have been used forcovering metal heart valve parts, pores of typical size 500 to 700microns have been provided and some tissue ingrowth has been observed.While the fabric covering has resulted in a decreased incidence ofthromboembolism, apparently due to the observed tissue ingrowth, suchvalves do suffer from other defects, notably wear of the fabric, causingcloth fragment embolism and chronic hemolytic anemia as a result ofturbulence of the blood over disrupted fabric coverings.

To date, the prior art has been unable to provide a heart valve whichnot only overcomes the thromboembolic problems of a smooth metal surfacebut also does not exhibit the wear failure problem of the prior artfabric covered heart valves.

SUMMARY OF THE INVENTION

The present invention is directed to cardiovascular prosthetic devicesor implants comprising a porous surface and a network of interconnectedinterstitial pores below the surface in fluid flow communication withthe surface pores. The provision of the porous surface and subsurfacenetwork promotes the formation of a smooth thin adherent tissue coatingon the porous surface rendering the same resistant to the formation ofblood clots normally associated with the presence of foreign bodies inthe blood stream.

The formation of the adherent tissue coating on the porous surface alsoallows the cardiovascular prosthetic device or implant of the presentinvention to be incorporated into the cardiovascular system, therebyachieving a more secure attachment than has previously been the case.

The tissue coating is formed by colonization of nucleated cellscirculating in the blood stream onto the porous surface and subsequentdifferentiation into other cell types. The tissue coating is formedrapidly over about a one-month period, does not appear to increasesignificantly in thickness thereafter and includes flattenedendothelial-like cells at the surface thereof.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a sectional view of a heart pacemaker electrode provided inaccordance with one embodiment of this invention.

GENERAL DESCRIPTION OF INVENTION

In U.S. Pat. No. 3,855,638, there is described a surgical prostheticdevice consisting of a metal substrate with a porous metal coating intowhich bone tissue may grow for incorporation of the prosthesis into thebody. The porous coating used in this prior art device has severalessential requirements, including restrictions on coating thickness,interstitial pore size and coating porosity. These parameters aredictated by the strength requirements of the surgical prosthetic device,namely, that the coating and the coating-substrate interface havestrengths at least that of bone, so that there is no danger of failureof the prosthesis after ingrowth of bone tissue.

In cardiovascular uses, however, strength is a less importantconsideration, and the ranges of parameters chosen are dictated to somedegree by the intended use of the prosthetic device or implant.

Further, the mechanism of incorporation of the surgical prostheticdevice of this prior art into the body is by ingrowth of tissue into thecoating while the present invention involves quite a different mechanismwhich arises from the different environment of the devices of theinvention as compared with that of the prior art.

The cardiovascular devices and implants provided in accordance with thisinvention fall broadly into two classes, namely, rigid items andflexible polymeric items, although there may be overlap between theclasses, as described in more detail below. For convenience, thespecific embodiments of the invention will be described within thegeneral framework of the two broad classes.

A. CARDIOVASCULAR DEVICES AND IMPLANTS CONSTRUCTED OF RIGID MATERIAL

The material of construction of the items in this class usually is ametal although other materials of construction may be used, such as,rigid polymeric material, ceramic material and carbon. Combination oftwo or more of the materials of construction may be used.

The general parameters of the porous surface for use in this class ofcardiovascular devices and implants of this invention may vary widelyand those chosen depend somewhat on the particular end use of theprosthetic device or implant, and specific parameters for certainspecific devices or implants are discussed in more detail below.

The porous surface intended to engage blood must have an interconnectednetwork of pores beneath the surface in fluid flow communication withthe surface pores to promote the colonization by nucleated cells andsubsequent differentiation into other cell types so that the tissuewhich is formed and grows into the surface is interlocked in thesubsurface network rendering the surface non-thrombogenic. The networkof pores preferably extends substantially throughout the body of theporous system.

The interstitial pore size may vary widely, generally from about 1micron up to about 1000 microns, although it may be preferred to usepore sizes below about 20 microns. The porosity also may vary widely,generally from about 8% by volume to the limit of coherence of theporous surface, and usually in the range of about 10 to about 50% byvolume.

The porous surface may be provided as part of a composite of a porouscoating embodying the surface on a coherent substrate in certainembodiments of the invention, although a wholly porous structure may beused. The thickness of the porous coating may vary from double layers ofparticles upwards, generally from about 1 to about 10,000 microns, thinlayers being preferred in devices having close tolerances.

The cardiovascular devices and implants should have adequate strength tomaintain their structural integrity under the physiological stresses ofthe environment in the body.

The materials of construction of the cardiovascular devices and implantsin this class of items should be non-toxic to blood and body tissue andbe otherwise biocompatible. This class of items will be describedparticularly with reference to metals, the term "metal" as used hereinincluding metal alloys, although it is understood that the parametersdescribed with respect to metals apply generally equally with respect tothe other materials of construction.

One suitable metallic material of construction is the cobalt alloy thatis known by the trade mark "VITALLIUM" while a further suitable materialis titanium.

The metal devices and implants in this class may be in the form of orinclude a rigid wholly porous system intended to engage blood and inwhich a network of interconnected pores extends substantially uniformlythroughout the body of the system and is defined by metallic particlesjoined to adjacent particles.

Alternatively, the metal devices and implants may include a rigidcomposite of a dense coherent metallic substrate and a rigid metallicporous coating intended to engage blood and which is adhered to thesubstrate and consists of metallic particles joined to adjacentparticles to form an interconnected network of pores which issubstantially uniformly distributed throughout the coating.

The rigid nature of the porous coating or porous system, the strength ofthe particle-particle bond and the strength of the substrate-coatinginterface in the case of the composite provide excellent wear andstrength characteristics in the cardiovascular implant or device. Theprecise parameters of the porous coating or system vary depending on theform of the device or implant, and specific values are discussed belowin connection with the specific embodiments of this class of item.

Metal particles making up the porous coating or system usually have aregular geometrical shape, such as spherical, but irregularly-shapedparticles alone, or in admixture with regularly-shaped particles, may beused.

SPECIFIC EMBODIMENTS OF RIGID CARDIOVASCULAR DEVICES AND IMPLANTS 1.HEART VALVE EMBODIMENT

One specific embodiment of the invention is a heart valve. Heart valvesinclude a plurality of components including an occluder, typically aball or disc which may be rigid or flexible, an occluder seating ring,occluder guide struts, optionally muscle guards to prevent interferenceby muscle with movement of the occluder, and a sewing ring to attach thevalve to the heart. The occluder seating ring, occluder guide struts andmuscle guards usually are constructed of metal. The occluder may bemetal or other material.

In accordance with this invention, the metallic blood engaging elementsof a heart valve are formed as composites of the type described aboveand having a dense coherent metallic substrate and a rigid metallicporous coating which is adhered to the substrate.

It is usual, however, to provide a polished metal surface in thoseblood-engaging portion of the valve where blood movement is sufficientto prevent the incidence of thrombus formation, such as, adjacent to theoccluder, where engagement between the occluder and other parts mayoccur and where tissue growth may interfere with occluder movement.

The proportion of the blood-engaging elements of the heart valve fromwhich the porous coating is omitted varies depending on the design ofthe heart valve but generally constitutes only a minor proportion of theblood-engaging elements.

The coating should be formed from fine metallic particles, usually of-325 mesh size and preferably of -500 mesh size, in order to minimizeabrasion between heart valve elements and hemolysis of the blood. It hasbeen found that porous coatings formed from finer particles providesmoother tissue coatings than porous coatings formed from coarserparticles.

It is also preferred to provide a thin porous coating on the metalsubstrate surfaces in order to provide the maximum orifice for bloodflow, and typically the thickness is about 20 to 300 microns, preferablyabout 50 to about 150 microns.

The shear strength of the composite surface is important, especiallywhere heart valve surfaces are in relative motion, and it is necessarythat the composite have a high fatigue tolerance, the endurance limit(10⁷ cycles) being greater than 500 psi. It is preferred for thesurface-coating interface and the coating itself to have shear strengthsgreater than about 1000 psi, more particularly greater than about 3000psi.

The porosity of the coating portion of the composite varies betweenabout 10 and about 50% by volume. Equivalent parameters are employed forother materials of construction.

The suture or sewing ring used in rigid metallic valves, particularlythose having the characteristics described above, may be provided in theform of a flexible polymeric material having a porous surfaceinterconnecting with a network of interconnected pores in thesubsurface. This structure represents one overlap between the classes ofstructure provided in accordance with this invention.

The porous polymeric material may be provided as the outer surface of aconventional foam filled fabric covered suture ring, attached theretodirectly or through an intermediate solid substrate.

It is preferred, however, to utilize a composite of the porous polymericmaterial and a coherent polymeric substrate as the sewing ring byproviding direct attachment between the polymeric substrate and theoccluder seating ring.

The attachment may be achieved by causing the solid substrate to flowinto a porous metal surface formed on the seating ring and harden in thesubsurface pores to interlock with the network of interconnected pores,for example, by pressure molding.

The latter procedure may be used, if desired, to provide flexible orrigid solid and/or porous plastic material coatings on rigid metalcoatings or other heart value components, by pressure molding a polymerto the metal coating.

Where a porous polymeric sewing ring is provided in accordance with theabove-described structure, the interstitial pore size is generally lessthan 200 microns while the porosity is about 10 to about 50% by volume.

2. PACEMAKER ELECTRODE EMBODIMENT

Another specific embodiment of the invention is a pacemaker electrodewhich is intended especially for location in the heart in engagementwith blood and tissue within the heart and for subjecting the heart totimed electrical impulses fed from a remote pacemaker.

As described in more detail below, electrodes of the type here describedmay also be used for electrical stimulation of the central or peripheralnervous system and body muscles.

In this specific embodiment, the pacemaker electrode preferably takesthe form of a composite of the above described form, comprising a densecoherent metal substrate and a rigid porous metal coating which isadhered to the substrate. Electrodes which are wholly porous also may beprovided.

The particles in the metallic coating generally have a particle size ofabout -100 mesh, preferably about -325 mesh and more preferably -500mesh. The coating has a porosity of about 10 to about 50% by volume andthe surface-coating interface and the coating itself have a shearstrength of greater than about 1000 psi to ensure adequate structuralstrength.

The thickness of the coating may vary widely up to about 500 microns,although a thickness in the range of about 20 to about 300 microns ispreferred. Equivalent parameters are employed for other materials ofconstruction.

A portion of the porous metal coating may be utilized to bond to theelectrode a polymer sleeve surrounding the current conducting wire. Thisbonding may be achieved by causing the sleeve polymer to flow into theporous metal surface and harden in the subsurface pores to interlockwith the network of interconnected pores, for example, by pressuremolding.

In some cases, it may be desirable to provide an outer polymericcoating, preferably a coating of a hydrophilic polymer having a poroussurface on the porous tip surface, rather than have the porous metalcoating exposed to blood and tissue. This polymeric coating may beprovided by the technique described above for joining the sleeve to theelectrode, for example, by pressure molding. If desired, the polymercoating may have a porous outer surface.

The electrode provided in accordance with this embodiment of theinvention may be in the form of a differential current densityelectrode. Electrodes of this type generally consist of a metalcurrent-carrying electrode surrounded by an insulating polymeric sleevewhich is spaced from a cylindrical end portion of the electrode todefine an electrolyte-containing chamber. A small number of holes extendthrough the polymer sleeve to the electrolyte-containing chamber.

This type of electrode achieves a very high current density at severalpoints on the surface thereof corresponding to the holes through thesleeve while utilizing a very low current density on the metalelectrode, thereby achieving the high current density required forefficient pacing while exerting only a low energy drain on the pacerbattery.

In accordance with this invention, the surface of the polymer sleeveconsists of an outer porous layer on a dense coherent substrate,permitting tissue formation and growth into the polymer sleeve. Thepolymer sleeve also may be joined to the metal electrode in thenon-spaced apart regions by using the technique described above forjoining a polymer sleeve to a metal electrode, for example, by pressuremolding.

The outer porous coating of such a differential current densityelectrode may have a thickness up to about 500 microns, although athickness in the range of about 20 to about 300 microns is preferred.The interstitial pore size is generally less than 200 microns with acoating porosity of about 10 to about 50% by volume.

Alternative structures of this type of electrode provide a wholly porouscylindrical metal electrode portion in the electrolytic chamber and theprovision of the outer sleeve in contact with the outer surface of awholly porous cylindrical metal electrode portion containingelectrolyte.

3. BLOOD PUMP EMBODIMENT

Another device utilizing a composite of the above described typecomprising a coherent substrate having an adherent porous coating overthe blood engaging surfaces thereof is a partially or totallyimplantable blood pump, such as, an artificial heart or ventricularassist device.

A blood pump generally possesses a housing having an inlet and anoutlet, valves located in the inlet and outlet to control the flow ofblood into and out of the housing and means for varying the internalvolume of the housing to achieve pumping motion from the inlet to theoutlet. The valves may be of the character and type already describedabove while the housing used is constructed of metal. The volume varyingmeans preferably is a flexible diaphragm, described in more detail belowwith respect to the class of flexible items.

In this embodiment, the porous metal coating usually has a thickness ofless than about 500 microns, preferably about 25 to about 300 microns.The particles forming the coating usually have a size of about -100mesh, preferably -325 mesh, and more preferably -500 mesh.

The metal coating has a porosity of about 10 to about 50% by volume andthe surface-coating interface and the coating itself has a shearstrength of greater than about 1000 psi to ensure adequate structuralstrength.

Equivalent parameters are employed for other materials of construction.

4. BLOOD STREAM FILTER EMBODIMENT

A further embodiment of this invention is a blood stream filter which isconstructed to prevent the passage therepast of blood clots present inthe blood stream.

Such filters generally are constructed of metal and comprise a filtermedium and support structure. In accordance with this invention, theblood engaging surfaces of the filter are formed of a composite of adense coherent metal substrate and a rigid metallic porous coating whichis adhered to the substrate.

The porous coating is usually formed of particles of size about -100mesh, preferably -325 mesh. The thickness of the coating on thesubstrate surface may vary widely up to about 500 microns, although itis preferred to employ a thickness of about 25 to about 300 microns.

The coating generally has a porosity of about 10 to about 50% and thesurface-coating interface and the coating itself has a shear strength ofgreater than about 1000 psi to ensure adequate structural strength.

Equivalent parameters may be employed with other materials ofconstruction.

5. BLOOD STREAM RELEASE CONTROL EMBODIMENT

The blood-engaging porous system provided in this invention may be usedto sample non-cellular material therethrough for the detection of thepresence and/or concentration of the constituents and/or for theconveying of material into the blood through the porous system.

In accordance with this embodiment, an artificial endocrine organ, suchas an artificial pancreas, may be provided.

The artificial pancreas possesses a chamber having a porous surfaceintended to interface with the blood and communicating with the interiorof the chamber. The chamber may contain pancreatic islet cells fordischarging insulin and/or glucagon to the blood stream through theporous surface. A semi-permeable membrane is located between the poroussurface and the cells within the chamber to prevent biological rejectionby the body.

Alternatively, the chamber may contain sensing devices and releasemechanisms permitting glucose to be sampled through the porous systeminterfacing with the flowing blood and insulin and/or glucagon to bereleased through the porous system and the tissue coating thereon intothe flowing blood. The source of the hormones and/or the controlcircuitry and/or the energy sources may be provided external to thebody, if desired, or may be implanted.

In accordance with this embodiment, a slow release device also may beprovided having a porous surface interfacing blood and communicatingwith a hollow interior containing a substance to be released through thesurface. Such a device provides slow, sustained release of the substanceinto the blood through the porous system and its associated tissuecoating interfacing the blood. The contents of the chamber of the devicemay be separated from the porous surface by a semi-permeable membrane asan aid in controlling the release of the substance. The substance may bea drug, for example for long term antibiotic therapy, or hormones, forexample, steroids providing a chronic implanted birth control device.

In the wholly porous system provided in such devices, the interstitialpore size may vary widely, for example, from about 1 micron up to about1000 microns. The porosity of the porous system may also vary widely,upwardly from about 8%, and usually in the range of about 10 to about50%.

The thickness of the porous system is not critical and may vary widely,for example, up to about 1 cm, although a thickness in the range ofabout 25 to about 500 microns usually is adopted.

Equivalent parameters are used for other materials of construction.

6. VASCULAR ACCESS TUBES

One such device is illustrated in FIG. 1. As seen therein, a pacemakerelectrode 10 has a coherent body portion 12 and a wholly porous tip 14comprising a plurality of small particles 16 sintered together to form atip 14. A cavity 18 is provided in the electrode 10 which houses a drug20 or other convenient substance, which is released through the poroustip 14 to heart tissue engaged by the electrode 10.

The blood engaging portions of vascular access tubes may be formed of acomposite of a dense coherent substrate and a rigid porous coating whichis adhered to the substrate, in accordance with a further specificembodiment of the invention.

Such vascular access tubes generally are metal, although rigid orflexible plastic materials also may be used. The access tubes may bepositioned wholly subcutaneously or transcutaneously as desired.

The particles in the metal coating generally have a particle size ofabout -100 mesh, preferably -325 mesh and more preferably -500 mesh. Thecoating has a porosity of about 10 to about 50% by volume and thesurface-coating interface and the coating itself have a shear strengthof greater than about 1000 psi to ensure adequate structural strength.

The coating may have a thickness which varies widely up to about 500microns, a thickness in the range of about 20 to about 300 microns beingpreferred. Equivalent parameters are employed with other materials ofconstruction.

MANUFACTURE OF COMPOSITE STRUCTURE IN METAL DEVICES AND IMPLANTS

The composite structure of many of the metal cardiovascular devices orimplants provided in accordance with this invention is formed by asintering procedure, in which a multiple number of layers of particlesare simultaneously formed on the substrate. Additional multiple layersmay be formed by further sintering.

The procedure involves roughening the smooth coherent substrate surfacewhere the coating is to be formed, forming a self-supporting coating ofa plurality of layers of metallic particles bound together and to thesubstrate by a suitable adhesive, drying the binder to provide a preformof dried coating on the substrate, and sintering the preform to causemetal fusion interconnection of the metal particles one with another andwith the roughened metal substrate.

In an alternative procedure, the preform may be formed from particles ofa metal compound which is readily thermally decomposable or a mixture ofsuch compounds and such particles which thermally decompose during thesintering step to provide the interconnection of the metal particleswith each other and to the substrate on sintering.

The precise sintering technique adopted depends to some extent on thesize of the particles from which the porous coating is formed andwhether the particles are in metal or metal compound form. The metal ofthe substrate and of the porous coating usually are the same, althoughdifferent metals may be used, if desired.

The metal and metal compound particles from which the porous coating isformed generally fall into one of four categories, namely -500 mesh(less than about 20μ), -325+500 mesh (about 20 to about 50μ), -100+325mesh (about 50 to about 200μ) and +100 mesh (greater than about +200μ).The term "mesh" used herein refers to the U.S. Standard Sieve mesh size.

The initial roughening of the smooth coherent substrate may be carriedout in any convenient manner, for example, by blasting with abrasivematerial. Thereafter, the coating of particles is formed on the surface.

In one procedure, a binder for the particles first is sprayed onto theroughened metal surface and the device then is suspended in a fluidizedbed of powder metal particles or powder metal compound particles to forma coating on the roughened surface. The coated body is withdrawn fromthe fluidized bed and the binder allowed to dry. This procedure has beenfound to be satisfactory for each of the particle sizes, except for the-500 mesh particles.

In an alternative procedure, the powder metal or metal compoundparticles are mixed with a binder to form a fairly viscous slurry whichis spray applied to the roughened surface to form the coating thereon,the coating thereafter being dried. It has been found that thisprocedure is satisfactory for -325 mesh size particles and below.

In a further procedure, the metal or metal compound particles and binderare slurried and the roughened surface is dipped into the slurry. Excessmaterial is allowed to run off and the coated body is dried.

Other methods of powder application may be adopted.

In each case, where the coating is formed from metal particles, afterthe formation of the dried coating on the substrate, the preform ofdried coating and substrate is sintered to cause metal fusioninterconnection of the metal particles one with another and with theroughened substrate surface to provide a rigid porous structureconsisting of multiple layers of particles having a network ofinterconnected pores substantially uniformly distributed throughout thecoating.

It is possible to build up any desired thickness of porous coating onthe coherent substrate by presintering the dried coating to provide somestrength thereto and then repeating the coating and presinteringoperation for as many cycles as is required to build up the desiredthickness. Each layer formed on the substrate contains a plurality oflayers of particles. When the desired thickness has been achieved, thecomposite is sintered to provide the required particle-particle andparticle-substrate bonds.

The presintering and sintering temperatures which are preferablyutilized depend on the particle size of the metal particles, lowertemperatures generally being used for smaller particle sizes.

Thus, for -500 mesh metal particles, presintering preferably is carriedout by heating at a temperature of about 2000° F. (about 1100° C.)momentarily or up to about 10 minutes and then cooling. Then, sinteringpreferably is carried out by heating at a temperature of about 2150° F.(about 1175° C.) for about 60 to about 90 minutes in a hydrogen or otherreducing gas atmosphere, or under vacuum.

For the -325 +500 mesh metal particles, presintering preferably iscarried out by heating at a temperature of about 2100° F. (about 1150°C.) for about 8 minutes, while sintering preferably is carried out byheating at a temperature of about 2200° F. (about 1200° C.) for about 60to about 90 minutes in a hydrogen or other reducing gas atmosphere, orunder vacuum.

When metal particles of particle size +325 mesh are used, thepresintering preferably is carried out at a temperature of about 2200°F. (about 1200° C.) and sintering preferably is carried out at atemperature of about 2200° to about 2300° F. (about 1200° C. to about1250° C.) for about 2 to about 3 hours, in a hydrogen or other reducinggas atmosphere, or under vacuum.

In the case where the coating is formed from thermally-decomposablemetal compound particles, the preform is heated to an elevatedtemperature to cause thermal decomposition of the metal compound and theformation of a porous coating of metal particles which are connectedtogether at their points of contact with each other and the substrate todefine a network of interconnected pores substantially uniformlydistributed throughout the coating.

The technique described above for the building up of layers of particlesto the required thickness may be adopted. The presintering and sinteringtemperatures which are preferably utilized correspond generally to thosefor metal particles of the same size.

The use of metal compounds in the sintering process is especiallybeneficial in those instances where particles of the metal itself cannotbe used at the desired particle size for any particular reason. Forexample, certain metals, such as titanium, are pyrophoric at smallparticle sizes.

Non-pyrophoric thermally-decomposable metal compounds, such as, thehydrides of those metals, then are used in place of the metal. Thisprocedure is particularly useful for making cardiovascular devices orimplants of titanium by thermal decomposition of titanium hydrideparticles on the metal substrate, for example, particles of -500 mesh.

Vacuum is usually used to withdraw the gas formed during the thermaldecomposition of the metal compound.

Following formation of the porous coating utilizing the abovetechniques, the coating may be machined and refined, if desired, toimprove its surface characteristics.

PRODUCTION OF WHOLLY POROUS METAL SYSTEMS

Wholly porous metallic devices and implants provided in accordance withthis invention may be formed by sintering metal particles or metalcompound particles in a mold at the sinter temperatures described abovefor the formation of porous coating layers, along with binders, ifnecessary.

B. CARDIOVASCULAR DEVICES AND IMPLANTS CONSTRUCTED OF FLEXIBLE POLYMERICMATERIAL

Flexible porous polymeric materials are used to provide thecardiovascular device or implant of this class. The polymeric materialused is a biocompatible synthetic polymeric material, preferably asegmented polyurethane and more preferably a segmented hydrophilicpolyurethane.

The general parameters of the porous surface for use in this class ofcardiovascular devices and implants of this invention may vary widelyand those chosen depend somewhat on the particular end use of theprosthetic device or implant, and specific parameters for certainspecific devices or implants are described in more detail below.

The porous surface of the flexible polymeric material must have aninterconnected network of pores beneath the surface in fluid flowcommunication with the surface pores to promote the colonization bynucleated cells and subsequent differentiation into other cell types sothat the tissue which is formed and grows into the surface isinterlocked in the subsurface network and renders the surfacenon-thrombogenic. The network of pores is preferably substantiallyuniformly distributed throughout the porous system.

The porous surface may be provided as part of a composite of a porouscoating embodying the surface and subsurface network on a coherentsubstrate in some embodiments while a wholly porous structure may beused in other embodiments.

SPECIFIC EMBODIMENTS OF FLEXIBLE POLYMERIC MATERIAL CARDIOVASCULARDEVICES AND IMPLANTS 1. SMALL BORE VASCULAR GRAFTS

Small bore vascular grafts comprise an elongate tubular body having aninside diameter from about 2 to about 6 mm, the diameter generallycorresponding to the diameter of the vessel to which the tube is to begrafted. The wall thickness of the graft may vary widely from about 0.2mm to about 1 mm or more.

The vascular grafts may be in the form of a single tube length or mayhave one or more integral branches to conform with the anatomicalrequirements of the graft.

The inner blood-engaging surface of the graft is porous and communicateswith a network of interconnected pores in the subsurface region. Theinterconnected pores preferably are substantially uniformly distributedthroughout the subsurface region. The pore size in the surface and thesubsurface region is generally less than about 50 microns and preferablyless than about 20 microns. The internal porosity promotes the formationof tissue on the surface, as described above in connection with therigid items provided in accordance with this invention.

The outer surface of the graft also is porous and communicates with anetwork of interconnected pores in the subsurface region, permittingingrowth of soft tissue from the surrounding body tissue, to incorporatethe graft permanently into the body.

The interstitial pore size of the outer porous region of the graft maybe the same as that of the inner porous region, but the pore sizes alsomay vary and in the outer porous region, pore sizes of up to about 200microns may be used.

The porosity of the inner and outer porous regions of the graft may varyfrom about 10 to about 70 vol. % consistent with the interconnectedporosity requirement for the subsurface regions.

The graft is required to have a minimum strength in use consistent withthe requirements that the graft may be sutured readily without tearingand that the graft have sufficient strength to prevent structuralbreakdown at the anastomosis and along the length of the graft.

The actual minimum strength requirements will vary depending on theintended use of the graft, the strength requirements for venous graftsbeing very much less than those for arterial grafts because of the lowervenous blood pressures. The grafts provided in accordance with thisembodiment of the invention for venous use should be able to withstandvenous blood pressure of not less than 25 mm Hg for prolonged periods,generally greater than one year, preferably greater than 5 years, in aphysiological environment.

The preferred aspect of this embodiment of the invention is theprovision of an arterial graft, which also may be used as a venousgraft, if desired, and such an arterial graft should be able towithstand pulsatile arterial blood pressure of greater than about 300 mmHg, preferably greater than about 500 mm Hg, for a prolonged period oftime, generally greater than one year, preferably greater than 5 years,in a physiological environment.

Consistent with these minimum strength requirements, the graft may havea wholly porous wall having a uniform pore size throughout, or a whollyporous wall in which the pore size varies in the inner and outer surfaceregions. Additionally, a dense coherent flexible polymeric substratelayer may be laminated between inner and outer porous layers.

In one preferred structure of the vascular graft, reinforcing materialis provided in association with the porous wall, and such reinforcingmaterial preferably takes the form of a fabric layer, such as a knittedDacron fabric layer laminated between inner and outer porous layers,although fibres, platelets and fillers also may be used as reinforcingagents.

2. LARGE BORE VASCULAR GRAFTS

Large bore vascular grafts differ from the small bore vascular graftsdescribed above in having an inside diameter greater than about 6 mm upto about 10 cm, although it is preferred for such grafts to have aninside diameter of less than about 5 cm.

The large bore vascular grafts also differ from the small bore grafts inthat the pore size of blood engaging surface and associated subsurfaceregion may vary up to about 200 microns, if desired, although it ispreferred to utilize the smaller pore size of less than 50 microns andmore preferably less than 20 microns.

The porosity and strength requirements of the large bore graft are thesame as those for the small bore graft referred to above. Additionally,in common with the small bore grafts, the large bore grafts may beprovided as a single tube or as a branched tube having one or moreintegral branches. Further, large bore grafts may be provided with oneor more integral small bore branches, if desired.

3. BLOOD PUMP DIAPHRAGMS

As described above in connection with the structure of blood pumps, aflexible diaphragm is generally used to achieve the internal volumetricchanges required to convey the blood through the pump.

In accordance with this embodiment of the invention, a blood pumpdiaphragm is provided in the form of an appropriately dimensioned planarsheet of flexible polymeric material having a porous surface intended toengage blood in the pump and in fluid flow communication with a networkof interconnected pores in a subsurface region. The wall thickness ofthe diaphragm may vary widely from about 0.2 mm to about 1.0 mm or more.The interconnected pores are preferably substantially uniformlydistributed throughout the subsurface region.

The porosity promotes the formation of tissue on the porous surface, asdescribed in detail above in connection with rigid items provided inaccordance with this invention.

The pore size in the surface and the subsurface region is less thanabout 200 microns, preferably less than about 50 microns and morepreferably less than about 20 microns, while the porosity may vary fromabout 10 to about 70 vol. %.

The diaphragm is required to have a minimum strength to preventstructural breakdown with use and to this end the diaphragm whenpositioned in the blood pump and the latter is located in aphysiological environment, should be able to withstand pulsatilearterial blood pressure of greater than about 300 mm Hg, preferablygreater than about 500 mm Hg, for a prolonged period of time, generallygreater than one year and preferably greater than about 5 years.

The diaphragm may be provided with a wholly porous structure or moreusually is formed as a composite of a porous coating which engages theblood bonded to a coherent flexible polymeric substrate.

The diaphragm also may have a porous subsurface region in whichreinforcement is provided, such as a layer of a fabric bonded to orwithin a porous layer.

4. VASCULAR AND INTRACARDIAC PATCHES

Vascular and intracardiac patches provided in accordance with thisembodiment of the invention take the form of a planar sheet of flexiblepolymeric material having a porous surface intended to engage blood inuse and in fluid flow communication with a network of interconnectedpores in a subsurface region, which are preferably substantiallyuniformly distributed throughout the subsurface region.

Porous surfaces generally are provided on both sides of the patches. Inthe case of the vascular patches, one side of the patch engages theblood to promote tissue ingrowth thereon while the other side engagessurrounding body tissue to promote ingrowth of soft tissue.

In the case of the intracardiac patches, blood engages both sides of thepatch within the heart and tissue grows on both sides from the blood.The wall thickness of the vascular and intracardiac patches may varywidely from about 0.2 mm to about 1.0 mm or more.

The pore size in the surfaces and the subsurface regions is less thanabout 200 microns, preferably less than about 50 microns, morepreferably less than about 20 microns, while the porosity may vary fromabout 10 to about 70 vol. %. Generally, the porosity is the same on bothsides of the patches, but may be varied, if desired.

The patch is required to have a minimum strength in use consistent withthe requirements that the patch may be sutured readily without tearingand that the patch have sufficient strength to prevent structuralbreakdown at the suture lines and over the area of the patch.

The minimum strength requirements of the patch will vary depending onits intended use. Thus, where the vascular patch is intended for venousrepair use only, the strength requirements are less than for vascularpatches which are intended for arterial repair use and for intracardiacpatches.

The vascular patches intended for venous use should be able to withstandvenous pressure of not less than 25 mm Hg for prolonged periods,generally greater than one year and preferably greater than 5 years in aphysiological environment, while the vascular patches intended forarterial use and the intracardiac patches should be able to withstandpulsatile arterial pressure of not less than about 300 mm Hg, andpreferably not less than about 500 mm Hg, for a prolonged period oftime, generally greater than one year, preferably greater than 5 years,in a physiological environment.

Consistent with these minimum strength requirements, the patch may bewholly porous with a uniform pore size throughout or may be whollyporous with differing pore sizes in different regions. Additionally, adense coherent flexible polymeric substrate layer may be laminatedbetween two porous face layers.

Preferably, a reinforcing material is provided in association with theporous material. Such reinforcing material preferably takes the form ofa fabric layer, such as, a knitted Dacron fabric layer, laminatedbetween two porous face layers, although fibres, platelets and fillersalso may be used as reinforcing agents.

5. FLEXIBLE HEART VALVE OCCLUDERS

Some heart valves employ flexible occluders, generally in the form offlaps, and in accordance with another embodiment of the invention, suchflap-type occluders take the form of an appropriately-dimensioned planarsheet of flexible polymeric material having porous surfaces intended toengage blood in use and in fluid flow communication with networks ofinterconnected pores in subsurface regions.

The planar sheet may be wholly porous with the interconnected poressubstantially uniformly distributed through the sheet or in the form ofa laminate of two outer porous layers bonded to an inner coherentflexible polymeric layer. A reinforcing material may be provided inassociation with the porous material, preferably in the form of a fabriclayer, such as, a knitted Dacron fabric layer, laminated between twoporous face layers.

The pore sizes in the porous structure is less than about 200 microns,preferably less than about 50 microns, and more preferably less thanabout 20 microns, while the porosity may vary from about 10 to about70%.

The flap is required to have a minimum strength in use consistent withthe requirements that the flap may be assembled with the remainder ofthe heart valve without tearing and that the flap have sufficientstrength to prevent structural breakdown in use. The wall thickness ofthe flap may vary widely from about 0.2 mm to about 1.0 mm or more.

PRODUCTION OF POROUS STRUCTURE IN POLYMERIC DEVICES AND IMPLANTS

A number of procedures may be used to produce polymeric cardiovasculardevices and implants having a porous structure therein according to thisinvention, either in rigid or flexible polymeric form.

The preferred procedure for forming the porous polymeric structure is touniformly disperse solvent-elutable particles in a continuous ordiscontinuous polymer phase, form a coherent shaped article from thedispersion wherein solvent-elutable particles are substantiallyuniformly dispersed throughout a continuous solid polymer phase ingenerally intraparticulate contact, and elute the solvent-elutableparticles from the article to provide a porous shaped product havinginterconnected pores therein.

The above-described porous polymer forming procedure may be effected ina number of different ways, the particular one chosen depending on theshape of product desired, the nature of the polymer used and the form ofthe product desired. One such procedure involves pulverizing a rigidpolymer to the desired particle size, mixing the powder with thesolvent-elutable particles, compressing the mixture, molding orextruding the mixture to the desired shape and leaching the solventelutable particles from the coherent shaped article to remove thesolvent-elutable particles.

Another specific procedure involves blending together a moldable and/orextrudable polymeric material and solvent-elutable particles insufficient quantities to provide a continuous phase of polymer and adispersed phase of solvent-elutable particles in the blend. Thereafter,the blend is molded or extruded to the desired shape and contacted withsolvent to remove the solvent-elutable particles and leave an opennetwork of interconnected pores throughout the body.

In a modification of this procedure, the polymer may be provided as asolution into which the solvent-elutable particles are mixed. Afterremoval of the solvent, the molding or extruding and leaching operationsare carried out.

Yet another specific procedure for forming the microporous polymerproduct involves initial formation of beads of polymer having a core ofsolvent-elutable material by polymer solution coating of the corematerial, compression molding or extruding of the beads to the desiredshape and product leaching to remove the solvent-elutable material.

A further specific procedure for the formation of a microporouspolymeric product includes forming a viscous casting solution of thepolymer, dispersing the solvent-elutable particles in the solution,casting the solution onto a casting surface and, after removal ofsolvent, eluting the solvent-elutable particles from the cast material.

Where it is desired by this procedure to form a porous tubular body, forexample, for use as a flexible blood vessel graft the viscous castingsolution is placed in a tube of inside diameter corresponding to theoutside diameter of the desired tube. A plumb ball or other suitabledevice, such as a rod, of diameter corresponding to the inside diameterof the article desired is drawn through the column of viscous material,resulting in the casting of the polymer on the inside of the tube.

Following drying of the casting, the polymer tube is removed, and theparticles eluted to provide the porous structure. Following the elutionstep, the structure of the device, including its porosity, may bemodified by heat treatment, such as, in an autoclave.

The porous polymeric structure formed by these procedures may be used assuch or in a lamination or composite structure with one or more coherentsolid rigid or flexible polymer substrates. Such composites or laminatesmay be formed by conventional techniques, using suitable bonding betweenthe porous material and the substrate.

Where it is desired to provide reinforcement to the porous material,such as, by way of a knitted fabric, as described above, such materialmay be incorporated into the structure by suitable modification to theporous structure-forming procedure.

COMBINATION WITH SOFT TISSUE INGROWTH

In many applications of the present invention, the promotion ofcolonization and tissue growth is accompanied by true soft tissueingrowth into the porous surface at the margins or on the outer surfacefrom adjacent body tissue, to provide bonding between the host and themember, as described in detail in my copending U.S. application Ser. No.752,603 filed Dec. 20, 1976.

The body tissue ingrowth combined with promotion of tissue growth on theporous surface from the nucleated blood stream cells is important inmany applications of the principles of the present invention.

For example, in an artificial heart constructed in accordance with thisinvention as described above, a porous coating externally as well asinternally provides a means of fixation of the artificial heart to hosttissues by soft tissue ingrowth into the external porous coating as wellas providing surfaces which are blood compatible arising fromcolonization and tissue formation on the blood-contacting surfaces.

Further, the vascular grafts provided in accordance with this inventionhave an outer porous layer, as described above, to provide for softtissue ingrowth and fixation of the graft into the body.

In the case of heart pacemaker electrodes, the electrodes are mainlypositioned against heart muscle which has considerable blood flowtherethrough, so that the tissue growth into the surface is acombination of true soft tissue ingrowth and growth arising from thenucleated blood stream cells.

SUMMARY

The present invention, therefore, provides novel cardiovascular devicesor implants which have biocompatibility and avoid the prior artthrombogenic problems. Modifications are possible within the scope ofthe invention.

What I claim is:
 1. A controlled release device in the form of a heartpacemaker electrode comprising a hollow chamber formed in said electrodecontaining a source of material to be released to heart tissue engagedby said electrode and a porous tissue-engaging surface of said electrodecommunicating with said chamber through a network of interconnectedpores, to permit said material to be released to said heart tissuethrough said network of interconnected pores, said porous surface beingformed of rigid electroconductive material inert to blood, said poroussurface having a porosity of at least 8% by volume up to the limit ofcoherence of the surface, an interstitial pore size of about 1 to about1000 microns and a thickness up to about 1 cm.
 2. The device of claim 1wherein said material is a hormone or a drug.
 3. The device of claim 1wherein said porosity is about 10 to about 50% by volume and saidthickness is about 25 to about 500 microns.
 4. The device of claim 1wherein the contents of said chamber are separated from said network ofinterconnected pores by a semi-permeable membrane.
 5. A controlledrelease device comprising a source of material to be released to bodytissue and a porous tissue-engaging surface communicating with saidmaterial through a network of interconnected pores to permit the same tobe released to tissue engaged by said surface, said porous surface beingformed or rigid electroconductive material inert to blood, said poroussurface having a porosity of at least 8% by volume up to the limit ofcoherence of the surface, an interstitial pore size of about 10 to about1000 microns and a thickness up to about 1 cm.